Pharmacological interventions for spasticity following spinal cord injury: results of a Cochrane systematic review.

UNLABELLED: The aim of this paper was to assess the effectiveness and safety of baclofen, dantrolene, tizanidine and any other drugs for the treatment of long-term spasticity in spinal cord injury (SCI) patients, as well as the effectiveness and safety of different routes of administration of baclofen. A systematic review of randomised controlled trials (RCTs), within the Cochrane Collaboration Injuries Group, was carried out. The Cochrane Injuries Group Specialised Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE and CINAHL were searched up to July 2006 without language restriction. Drug companies and experts active in the area were also contacted to find other relevant studies. Two investigators independently identified relevant studies, extracted data and assessed methodological quality of studies resolving disagreement by consensus. Nine out of 55 studies met the inclusion criteria. The heterogeneity among studies did not allow quantitative combination of RESULTS: Study designs were: 8 crossover, 1 parallel-group trial. Two studies (14 SCI patients) showed a significant effect of intrathecal baclofen in reducing spasticity (Ashworth score and activities of daily living [ADL] performances), compared to placebo, without any adverse effect. The study comparing tizanidine to placebo (118 SCI patients) showed a significant effect of tizanidine in improving Ashworth score but not in ADL performances. The tizanidine group reported significant rates of adverse effects (drowsiness, xerostomia). For the other drugs (gabapentine, clonidine, diazepam, amytal and oral baclofen) the results do not provide evidence for a clinical significant effectiveness. This systematic review indicates that there is insufficient evidence to assist clinicians in a rational approach to antispastic treatment for SCI. Further research is urgently needed to improve the scientific basis of patient care.

Follow-up strategies for women treated for early breast cancer.

BACKGROUND: Follow-up examinations are commonly performed after primary treatment for women with breast cancer. They are used to detect recurrences at an early (asymptomatic) stage. OBJECTIVES: To assess the effectiveness of different policies of follow-up for distant metastases on mortality, morbidity and quality of life in women treated for stage I, II or III breast cancer. SEARCH STRATEGY: We searched, the Breast Cancer Group's specialized register (May 14, 2004), the Cochrane Controlled Trial Register (Cochrane Library Issue 1, 2004), Medline (January 1966 - May 2004) and EMBASE (1988 - May 2004). References from retrieved articles were also checked. SELECTION CRITERIA: All randomised controlled trials (RCTs) assessing the effectiveness of different policies of follow-up after primary treatment were reviewed for inclusion. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and eligibility for inclusion in the review. Data were pooled in an individual patient data meta-analysis for the two RCTs testing the effectiveness of different follow-up schemes. Subgroup analyses were conducted by age, tumour size and lymph node status. MAIN RESULTS: Four RCTs involving 3055 women with breast cancer (clinical stage I, II or III) were included. Two of these involving 2563 women compared follow-up based on clinical visits and mammography with a more intensive scheme including radiological and laboratory tests. After pooling the data, no significant differences in overall survival (hazard ratio 0.96, 95% confidence interval 0.80 to 1.15) or disease-free survival (hazard ratio 0.84, 95% confidence interval 0.71 to 1.00) emerged. No differences in overall survival and disease-free survival emerged in subgroup analyses according to patient age, tumour size and lymph node status before primary treatment. In 1999, 10-year follow-up data became available for Rosselli Del Turco and no significant differences in overall survival were found. One RCT (296 women) compared follow-up performed by a hospital-based specialist to follow-up performed by general practitioners. No significant differences in time to detection of recurrence and quality of life emerged. Patient satisfaction was greater among patients treated by general practitioners. One RCT (196 women) compared regularly scheduled follow-up visits to less frequent visits restricted to the time of mammography. No significant differences emerged in interim use of telephone and frequency of GP's consultations. AUTHORS' CONCLUSIONS: This updated review of RCTs conducted almost 20 years ago suggest that follow-up programs based on regular physical examinations and yearly mammography alone are as effective as more intensive approaches based on regular performance of laboratory and instrumental tests in terms of timeliness of recurrence detection, overall survival and quality of life. In one RCT, follow-up care performed by trained general practitioners working in an organized practice setting had comparable effectiveness to that delivered by hospital-based specialists in terms of quality of life and time to detection of distant metastases.

Antibiotic prophylaxis in intensive care units: meta-analyses versus clinical practice.

OBJECTIVE: At least 7 meta-analyses (MA) have been published since 1991 on the effectiveness of antibiotic prophylaxis in Intensive care units (ICU) patients, but controversy still remains about the overall effectiveness and risk-benefits profile of the treatment. This paper aims to summarise available data on effectiveness and discuss reasons why the controversy is still open and possible directions for future research. DESIGN: Review of available published MA on the effectiveness of various regimens of antibiotic prophylaxis with particular emphasis on the results of the individual patient data analysis published in 1998. SETTING: MA or randomised control trials (RCTs), published and unpublished, conducted anywhere in the world. PATIENTS AND PARTICIPANTS: Unselected adult ICU populations included in studies, published and unpublished, comparing different forms of antibiotic prophylaxis. MAIN OUTCOME MEASURE: Respiratory tract infections (RTIs) - however defined in individual studies - and total mortality. DATA SOURCES: General information from the 7 MAs published between 1991 and 1999 and detailed information from the MA published in the British Medical Journal in 1998 that reported data on 5727 patients enrolled in 33 RCTs; access to individual patients data could be obtained from 25 of 33 RCTs and allowed a confirmatory individual patient MA on 4343 patients. RESULTS: Pooled estimates from 16 RCTs (including 3361 patients) testing the effect of the topical and systemic antibiotic combination indicates a significant reduction of both RTIs (OR=0.35, 95% CI=0.29-0.41) and total mortality (OR=0.80, 95% CI=0.69-0.93). Five and 23 patients need to be treated to prevent one infection and one death, respectively, using this treatment. Pooled data from the 17 RCTs (including 2366 patients) testing the effect of a regimen based on topical antimicrobials indicated a statistically significant reduction in RTIs (OR=0.57, 95% CI=0.46-0.69) but not in total mortality (OR=1.01; 95% CI=0.84-1.22). Individual patient data analyses confirmed these results. CONCLUSIONS: After over 30 RCTs and seven MAs, there is strong evidence that antibiotic prophylaxis can reduce both RTIs and total mortality in ICUs patients in a statistically and clinically significant way. Concerns about the possible occurrence of antimicrobial resistance are not supported by available data but cannot, at the same time, be ruled out due to methodologic inadequacies of the studies carried out so far. Whether new trials are needed, and how they should be designed to answer the question of the potential for antibiotic resistance following widespread use of the treatment, are now the main issues to be settled. Convening an international panel of clinical experts and methodologists could be appropriate, in order to explore the best way to resolve the controversy that seems to be preventing the widespread use of a treatment that the best analysis of available data now indicates is effective.

Pharmacological interventions for spasticity following spinal cord injury.

BACKGROUND: Spasticity is a major health problem for patients with a spinal cord injury (SCI) that limits patients' mobility and affects independence in activities of daily living and work. Spasticity may also cause pain, loss of range of motion, contractures, sleep disorders and impair ambulation in patients with an incomplete lesion. The effectiveness of available drugs is still uncertain and they may cause adverse effects. Assessing what works in this area is complicated by the lack of valid and reliable measurement tools. The aim of this systematic review is to critically appraise and summarise existing information of the effectiveness of available treatments and to identify areas where further research is needed. OBJECTIVES: To assess the effectiveness and safety of Baclofen, Dantrolene, Tizanidine and any other drugs for the treatment of long term spasticity in SCI patients as well as the effectiveness and safety of different routes of administration of Baclofen. SEARCH STRATEGY: We searched the Injuries Group specialised register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE and CINHALH up to 1998. Drug companies and experts active in the area were also contacted. SELECTION CRITERIA: All parallel and crossover RCTs including spinal cord injury patients complaining of "severe spasticity". Studies where less than 50% of patients had a spinal cord injury were excluded. DATA COLLECTION AND ANALYSIS: Methodological quality of studies (allocation concealment, blinding, patients characteristics, inclusion and exclusion criteria; interventions; outcomes; lost to follow up) was independently assessed by two investigators. The heterogeneity among studies did not allow quantitative combination of results. MAIN RESULTS: Nine out of 53 studies met the inclusion criteria. Study design was: 8 cross over, 1 parallel-group trial. Two studies (14 SCI patients), showed a significant effect of intrathecal baclofen in reducing spasticity (Ashworth Score and ADL performances), compared to placebo, without any side effect. The study comparing tizanidine to placebo (118 SCI patients) showed a significant effect of tizanidine in improving Ashworth Score but not in ADL performances. Tizanidine group reported significant rates of adverse effects (drowsiness, xerostomia). For the other drugs (Gabapentine, Clonidine, Diazepam, Amytal and oral Baclofen ) the results do not provide evidence for a clinical significant effectiveness. REVIEWER'S CONCLUSIONS: There is insufficient evidence to assist clinicians in a rational approach to antispastic treatment for SCI. Further research is urgently needed to improve the scientific basis of patient care.

Sensory stimulation for brain injured individuals in coma or vegetative state.

BACKGROUND: Coma and vegetative state follow traumatic brain injury in about one out of eight patients, and in patients with non traumatic injury the prognosis is worse. The use of sensory stimulation for coma and vegetative state has gained popularity during the 1980's but beliefs and opinions about its effectiveness vary substantially among health professionals. OBJECTIVES: To assess the effectiveness of sensory stimulation programmes in patients in coma or vegetative state. SEARCH STRATEGY: We searched the Injuries Group specialised register, the Cochrane Controlled trials register, EMBASE, MEDLINE, CINAHL and PSYCHLIT from 1966 to January 2002, without language restriction. Reference lists of articles were scanned and we contacted experts in the area to find other relevant studies. SELECTION CRITERIA: Randomised or controlled trials that compared sensory stimulation programmes with standard rehabilitation in patients in coma or vegetative state. DATA COLLECTION AND ANALYSIS: Abstracts and papers found were screened by one reviewer. Three reviewers independently identified relevant studies, extracted data and assessed study quality resolving disagreement by consensus. MAIN RESULTS: Three studies were identified with 68 patients in total. The overall methodological quality was poor and studies differed widely in terms of outcomes measures, study design and conduct. We therefore did not carry out any quantitative synthesis but reviewed results of available studies qualitatively. REVIEWER'S CONCLUSIONS: This systematic review indicates that there is no reliable evidence to support, or rule out, the effectiveness of multisensory programmes in patients in coma or vegetative state.

Follow-up strategies for women treated for early breast cancer.

BACKGROUND: Follow-up examinations are commonly performed after primary treatment for women with breast cancer. They are used to detect recurrences at an early (asymptomatic) stage. OBJECTIVES: To assess the effectiveness of different policies of follow-up for distant metastases on mortality, morbidity and quality of life in women treated for early breast cancer. SEARCH STRATEGY: We searched the Breast Cancer Groups specialised register, the Cochrane Controlled Trials Register ( Cochrane Library Issue 4, 1999), MEDLINE (January 1975-September 1999) and EMBASE (1988-September 1999) using "Breast Neoplasms" and "follow-up". References from retrieved articles were also checked, as were the lists of presentations from recent breast cancer meetings. SELECTION CRITERIA: All randomised controlled trials (RCTs) assessing the effectiveness of different policies of follow-up after primary treatment were reviewed for inclusion. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and eligibility for inclusion in the review. Data were pooled in an individual patient data meta-analysis for the two RCTs testing the effectiveness of different follow-up schemes. Subgroup analyses by age, tumour size and lymph node status before primary treatment are also presented. MAIN RESULTS: Four RCTs involving 3204 women with early breast cancer (clinical stage I, II or III) have been included. Two RCTs involving 2563 women compared follow-up based on clinical visits and mammography with a more intensive scheme including radiological and laboratory tests. After pooling the data, no significant differences in overall survival (hazard ratio 0.96, 95% confidence interval 0.80 to 1.15) or disease-free survival (hazard ratio 0.84, 95% confidence interval 0.71 to 1.00) emerged. No differences in overall survival and disease-free survival emerged in subgroup analyses according to patient age, tumour size and lymph node status before primary treatment. One RCT (296 women) compared follow-up performed by a hospital-based specialist to follow-up performed by general practitioners. No significant differences in time to detection of recurrence and quality of life emerged. One RCT (196 women) compared regularly scheduled follow-up visits to less frequent visits restricted to the time of mammography. No significant differences emerged in interim use of telephone and frequency of GP's consultations. REVIEWER'S CONCLUSIONS: Follow-up programs based on regular physical examinations and yearly mammography alone appear to be as effective as more intensive approaches based on regular performance of laboratory and instrumental tests in terms of timeliness of recurrence detection, overall survival and quality of life. In one RCT, follow up care performed by general practitioners had comparable effectiveness to that delivered by hospital based specialists in terms of quality of life and time to detection of distant metastases.

Evidence-based medicine and its horizons: a useful tool for nephrologists?

Though the concept of 'evidence-based medicine' (EBM) nowadays has become very popular and even fashionable, its practice is far from being an established reality. There are many reasons why, despite its potential, EBM finds obstacles in expressing its full potential as a tool to better inform health care decisions. Broadly speaking, these obstacles fall into three categories: (i) inadequacy of available information with respect the complexities of health care delivery; (ii) poor quality of clinical research; and (iii) insufficient and inappropriate efforts to promote the uptake of effective interventions in clinical practice. In the first part of the paper, we will discuss: (i) what evidence-based medicine is; (ii) why systematic reviews are the fundamental tool of EBM and what is really special about them; (iii) what are the tools for the practice of EBM; (iv) what its limitations are; and (v) what are the hindrances to its implementation. In the second part, a brief assessment of the state of the art of systematic reviews in nephrology will be presented, with special reference to the activities of the recently launched Cochrane Collaborative Review Group in Renal Diseases.

Evidence-based medicine and practice: what's new for the physicians?

This paper introduces the readers to the concepts of Evidence-Based Medicine (EBM) and Evidence-Based Health Care (EBHC). After taking the view that EBM and EBHC are essentially a new way of thinking about the theory and practice of medicine, the paper discusses their potential, limitation and ambiguities. Besides summarising the roles of EBM and EBHC in providing information relevant for patient care, medical education, health policy-making, information-seeking and eventually, guideline production, the paper closes discussing some of the potentials as well as dangers of this new scientific and cultural movement.

The Cochrane collaboration in neurology: acquisitions, research, and new initiatives.

The Cochrane Collaboration (CC) is an international organization involving 16 national centers around the world, set up in response to the need for collecting all randomized controlled trials on health care interventions, with the aim of facilitating and coordinating the preparation, maintenance and dissemination of periodic systematic reviews of these trials. These are prepared by Collaborative Review Groups (CRGs) working together in an area of common interest under the guidance of an editorial team, supported by national Cochrane centers. Nine CRGs are involved in each neurological field, with more than 300 reviewers and members of editorial teams. For a review to be called a 'Cochrane review', it must be structured in the format outlined in the Cochrane Handbook. It is then published and disseminated through the Cochrane Database of Systematic Reviews (CDSR) in the Cochrane Library (CL). Each Cochrane review is prepared using the Review Manager software distributed to CRGs by CC. The editorial team is responsible for assembling an edited module of reviews prepared by CRGs for incorporation and dissemination using electronic media through the CDSR located in the CL. The CL contains information about the CC and 4 other databases: the Database of Abstracts of Reviews of Effectiveness, the Cochrane Controlled Trials Register, the Cochrane Review Methodology Database and the NHS Economic Evaluation Database. The authors use an example of Cochrane reviews about cerebrovascular disorders to illustrate that the CL is a powerful source of evidence for answering clinical questions and providing information as a basis for therapeutic decisions, for the improvement of neurological practice. A new initiative, the Cochrane Neurological Network, has recently been set up with the aim of improving communication among neurological CRGs, and between them and health care professionals interested in neurological diseases so as to update neurologists on the activity of the CC.

Functional status in patients with spinal cord injury: a new standardized measurement scale. Gruppo Interdisciplinare Valutazione Interventi Riabilitativi.

OBJECTIVE: To report on the validation process of a new functional assessment scale (Valutazione Funzionale Mielolesi [VFM]) for patients with spinal cord injury (SCI). DESIGN: Prospective study testing for the VFM in a sample of patients with SCI to evaluate the scale characteristics in terms of psychometric and clinical validity. SETTING: Eight SCI units located in northern Italy. PATIENTS: One hundred patients were recruited and followed up for 18 months. Seventy-seven subjects were men, subjects' mean age was 37 years, 67 were paraplegic, and for 81 their SCI was of traumatic etiology. MAIN OUTCOME MEASURES: VFM's characteristics are described using estimates of construct and criterion validity (estimates of the strength and direction of associations between different VFM tasks and between VFM and other medical and nonmedical variables). The Barthel index was used as concurrent and independent measure. RESULTS: VFM met all psychometric criteria usually recommended and, at least in the current sample, was found to be strongly correlated with independent clinical variables (diagnosis and lesion level) and with the Barthel index. Moreover, most of the domains were able to document large and significant changes over time. CONCLUSIONS: VFM is a reliable and valid tool that can be used confidently in the rehabilitation setting for patients with SCI to screen for functional problems and monitor changes in patients' functional status and impact of rehabilitation.